Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt
- Eötvös Loránd University, Hungary
- Hungarian Academy of Sciences, Hungary
Abstract
Two related multisubunit tethering complexes promote endolysosomal trafficking in all eukaryotes: Rab5-binding CORVET that was suggested to transform into Rab7-binding HOPS. We have previously identified miniCORVET, containing Drosophila Vps8 and three shared core proteins, which is required for endosome maturation upstream of HOPS in highly endocytic cells (Lorincz et al., 2016a). Here we show that Vps8 overexpression inhibits HOPS-dependent trafficking routes including late endosome maturation, autophagosome-lysosome fusion, crinophagy and lysosome-related organelle formation. Mechanistically, Vps8 overexpression abolishes the late endosomal localization of HOPS-specific Vps41/Lt and prevents HOPS assembly. Proper ratio of Vps8 to Vps41 is thus critical because Vps8 negatively regulates HOPS by outcompeting Vps41. Endosomal recruitment of miniCORVET- or HOPS-specific subunits requires proper complex assembly, and Vps8/miniCORVET is dispensable for autophagy, crinophagy and lysosomal biogenesis. These data together indicate the recruitment of these complexes to target membranes independent of each other in Drosophila, rather than their transformation during vesicle maturation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Zsófia Simon-Vecsei
Funding
Magyar Tudományos Akadémia (LP-2014/2)
- Gábor Juhász
Ministry of Human Capacities of Hungary (ÚNKP-18-4-ELTE-409)
- Zsófia Simon-Vecsei
Magyar Tudományos Akadémia (PPD-222/2018)
- Péter Lőrincz
Magyar Tudományos Akadémia (BO/00652/17)
- Zsófia Simon-Vecsei
National Research, Development and Innovation Office of Hungary (GINOP-2.3.2-15-2016-00006)
- Gábor Juhász
National Research, Development and Innovation Office of Hungary (GINOP-2.3.2-15-2016-00032)
- Gábor Juhász
National Research, Development and Innovation Office of Hungary (K119842)
- Gábor Juhász
National Research, Development and Innovation Office of Hungary (KKP129797)
- Gábor Juhász
National Research, Development and Innovation Office of Hungary (PD124594)
- Zsófia Simon-Vecsei
Ministry of Human Capacities of Hungary (ÚNKP-18-2-II-ELTE-32)
- Lili Anna Kenéz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alexey J Merz, University of Washington School of Medicine, United States
Version history
- Received: January 31, 2019
- Accepted: June 13, 2019
- Accepted Manuscript published: June 13, 2019 (version 1)
- Version of Record published: June 25, 2019 (version 2)
Copyright
© 2019, Lőrincz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt
eLife 8:e45631.
https://doi.org/10.7554/eLife.45631
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